Retinal cyclodextrin acetals and hemiacetals for treating skin complexion disorder

Abstract

The present invention discloses certain polyene cyclodextrin acetals and hemiacetals that are effective in providing skin clarification, which is useful for the treatment of acne, and skin disfigurements and skin darkening resulting from acne; skin darkening from cancer, diabetes, radiation treatments, chemotherapy, and sun-burn; mitochondrial and DNA dysfunction; age spots; loss of cellular antioxidants; skin changes associated with aging including collagen loss, loss of skin pliability, loss of skin suppleness, skin wrinkles and fine lines, oxidation, damage from radiation, damage from free radicals, and damage from UV; dry skin; xerosis; ichthyosis; dandruff; brownish spots; keratoses; melasma; lentigines; liver spots; skin pigmentation including pigmented spots, dark circles under the eyes, darkened skin, and blemishes; oily skin; warts; eczema; pruritic skin; psoriasis; inflammatory dermatoses; topical inflammation; disturbed keratinization; scalp dryness, and combinations thereof.

The invention claimed is: 
     
       1. A compound of formula (I), or an isomer thereof; 
       
         
           
           
               
               
           
         
         wherein, 
         n=0 to 4, and 
         X=a direct bond, —CH 2 —CH 2 —O—, or —CH 2 —CH 2 —CH 2 —O—, and 
         Z═H, —CH 2 —CH 2 —OH, —CH 2 —CH 2 —CH 2 —OH, —SO 3 H, 
         —SO 3 M, —PO 3 H 2 , —PO 3 M, or —PO 3 M 2 , and 
         R=a retinoid, or a carotenoid, and 
         M=Na, K, Ca, Mg, Ba, Zn, Mn, Cu, Fe, Co, or Ni. 
       
     
     
       2. The compound of  claim 1 , wherein n is 1, 2, or 3, and X is a direct bond. 
     
     
       3. The compound of  claim 1 , wherein R is selected from the group consisting of: 
       
         
           
           
               
               
           
         
         wherein, 
         Y=point of attachment. 
       
     
     
       4. The compound of  claim 1 , wherein said compound is of formula (II); 
       
         
           
           
               
               
           
         
         wherein, 
         n=3. 
       
     
     
       5. A composition comprising a compound of  claim 1 . 
     
     
       6. A composition comprising a compound of  claim 1 , wherein said composition treats an ailment related to skin complexion. 
     
     
       7. A composition comprising a compound of  claim 1 , wherein said composition comprises a pharmaceutical, nutraceutical, or cosmetic composition. 
     
     
       8. The composition of  claim 7 , wherein said composition further comprises  Lonicera caprifolium  flower extract, or  Lonicera japonica  flower extract, or combinations thereof. 
     
     
       9. A composition comprising a compound of  claim 1 , wherein said composition further comprises water, emulsifying wax, ensulizol, octinoxate, propyleene glycol, gluconolactone, sodium benzoate, triethanolamine, ammolnium acryloyldimethyltaurate/VP copolymer, titanium dioxide, and combinations thereof. 
     
     
       10. A composition comprising a compound of  claim 1 , wherein said composition further comprises water, hydroxypropyl starch phosphate, candelilla wax, jojoba wax, rice bran polyglyceryl esters, glyceryl stearate, cetearyl alcohol, sodium stearoyl lactate, polyglyceryl-10 pentastearate, behenyl alcohol, glycerin, cetyl alcohol, stearyl alcohol, isostearyl neopentanoate,  Lonicera caprifolium  flower extract,  Lonicera japonica  flower extract, and combinations thereof. 
     
     
       11. A composition comprising a compound of  claim 1 , wherein said composition further comprises water, carbopol,  Lonicera caprifolium  flower extract,  Lonicera japonica  flower extract, and combinations thereof. 
     
     
       12. A method of treating, reducing the occurrence of, or improving the symptoms associated with a condition selected from the group consisting of: acne and skin darkening; age spots; loss of cellular antioxidants; skin changes associated with aging including collagen loss; loss of skin pliability; loss of skin suppleness; skin wrinkles and fine lines; damage from radiation and damage from free radicals; dry skin; xerosis; ichthyosis; dandruff; keratoses; melasma; lentigines; liver spots; skin pigmentation; pigmented spots, dark circles under the eyes, darkened skin, and blemishes; oily skin; warts; eczema; pruritic skin; psoriasis; inflammatory dermatoses; topical inflammation; scalp dryness and combinations thereof; which comprises administering the compound of  claim 1  to a subject in need thereof. 
     
     
       13. The composition of  claim 5 , wherein said composition comprises a topically administrable or orally administrable composition. 
     
     
       14. The method of  claim 12 , wherein the condition is acne and skin darkening. 
     
     
       15. The method of  claim 12 , wherein the condition is skin wrinkles and fine lines. 
     
     
       16. A process for making a compound of  claim 1 , wherein said process comprises (i) first mixing a polyene aldehyde and an organic solubilizing liquid until a transparent mixture is obtained; (ii) to this mixture a suitable cyclodextrin and water are added and mixed for 1-120 hours under a nitrogen or argon atmosphere; (iii) the reaction mixture is then dried to a powder; (iv) the preferred method of drying is spray drying.